Metabolic subtypes and immune landscapes in esophageal squamous cell carcinoma: prognostic implications and potential for personalized therapies.

BACKGROUND: This study aimed to identify metabolic subtypes in ESCA, explore their relationship with immune landscapes, and establish a metabolic index for accurate prognosis assessment. METHODS: Clinical, SNP, and RNA-seq data were collected from 80 ESCA patients from the TCGA database and RNA-seq data from the GSE19417 dataset. Metabolic genes associated with overall survival (OS) and progression-free survival (PFS) were selected, and k-means clustering was performed. Immune-related pathways, immune infiltration, and response to immunotherapy were predicted using bioinformatic algorithms. Weighted gene co-expression network analysis (WGCNA) was conducted to identify metabolic genes associated with co-expression modules. Lastly, cell culture and functional analysis were performed using patient tissue samples and ESCA cell lines to verify the identified genes and their roles. RESULTS: Molecular subtypes were identified based on the expression profiles of metabolic genes, and univariate survival analysis revealed 163 metabolic genes associated with ESCA prognosis. Consensus clustering analysis classified ESCA samples into three distinct subtypes, with MC1 showing the poorest prognosis and MC3 having the best prognosis. The subtypes also exhibited significant differences in immune cell infiltration, with MC3 showing the highest scores. Additionally, the MC3 subtype demonstrated the poorest response to immunotherapy, while the MC1 subtype was the most sensitive. WGCNA analysis identified gene modules associated with the metabolic index, with SLC5A1, NT5DC4, and MTHFD2 emerging as prognostic markers. Gene and protein expression analysis validated the upregulation of MTHFD2 in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA. CONCLUSION: The established metabolic index and identified metabolic genes offer potential for prognostic assessment and personalized therapeutic interventions for ESCA, underscoring the importance of targeting metabolism-immune interactions in ESCA. MTHFD2 promotes the progression of ESCA and may be a potential therapeutic target for ESCA.

Fluorescence enhancement of surface plasmon coupled emission by Au nanobipyramids and its modulation effect on multi-wavelength radiation.

Surface plasmon coupled emission (SPCE), a novel surface-enhanced fluorescence technique, can generate directional and amplified radiation by the intense interaction between fluorophores and surface plasmons (SPs) of metallic nanofilms. For plasmon-based optical systems, the strong interaction between localized and propagating SPs and "hot spot" structures show great potential to significantly improve the electromagnetic (EM) field and modulate optical properties. Au nanobipyramids (NBPs) with two sharp apexes to enhance and restrict the EM field were introduced through electrostatic adsorption to achieve a mediated fluorescence system, and the emission signal enhancement was realized by factors over 60 compared with the normal SPCE. It has been demonstrated that the intense EM field produced by the NBPs assembly is what triggered the unique enhancement of SPCE by Au NBPs, which effectively overcomes the inherent signal quenching of SPCE for ultrathin sample detection. This remarkable enhanced strategy offers the chance to improve the detection sensitivity for plasmon-based biosensing and detection systems, and expand the range of applications for SPCE in bioimaging with more comprehensive and detailed information acquisition. The enhancement efficiency for various emission wavelengths was investigated in light of the wavelength resolution of SPCE, and it was discovered that enhanced emission for multi-wavelength could be successfully detected through the different emission angles due to the angular displacement caused by wavelength change. Benefit from this, the Au NBP modulated SPCE system was employed for multi-wavelength simultaneous enhancement detection under a single collection angle, which could broaden the application of SPCE in simultaneous sensing and imaging for multi-analytes, and expected to be used for high throughput detection of multi-component analysis.

[Expression of SIL-2R in Patients with Multiple Myeloma and Its Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significance of soluble interleukin-2 receptor(sIL-2R) in patients with multiple myeloma(MM). METHODS: 54 newly diagnosed MM patients in the Second Affiliated Hospital of Fujian Medical University from February 2020 to December 2021 were selected as the observation group, and 60 healthy people in our hospital in the same period were selected as the control group. The expression levels of sIL-2R in the serum of the two groups were detected by enzyme-linked immunosorbent assay. The differences of sIL-2R expression level among different clinical parameter groups in MM patients were compared. The clinical parameters include:gender, age, ISS stage, hemoglobin, albumin, serum creatinine, lactate dehydrogenase and ß2-microglobulin, blood calcium, bone marrow plasma cell ratio and treatment response. The relationship between sIL-2R expression level and progression-free survival(PFS) and overall survival(OS) in MM patients were analyzed. RESULTS: The expression of serum SIL-2R in MM patients was significantly higher than that in healthy control group (P<0.05). The expression of sIL-2R in MM patients who did not achieve complete remission(CR) was significantly higher than those of CR patients (P=0.037). There was no significant difference in the expression of serum sIL-2R between the groups of different sex, age, ISS stage, hemoglobin concentration, albumin content, serum creatinine level, lactate dehydrogenase level, the content of ß2-microglobulin, the concentration of blood calcium, and the proportion of bone marrow plasma cells(P>0.05). The PFS of sIL-2R high expression group(15 months) was shorter than that of sIL-2R low expression group (22 months), which was significant difference (P=0.041). But there was no significant difference in OS between sIL-2R high expression group and sIL-2R low expression group (P=0.124). Univariate analysis results showed that the high expression of serum sIL-2R was associated with poor PFS in MM patients. Multivariate analysis results showed that the high expression of serum sIL-2R was still an independent adverse prognostic factor for PFS in MM patients, However, the expression of serum sIL-2R was not statistically significant in evaluating OS in MM patients by univariate and multivariate analysis. CONCLUSION: The expression of serum sIL-2R in MM patients was significantly higher than that in healthy people. Serum sIL-2R is an independent prognostic factor of PFS in MM patients.

Addition of hyperbaric oxygen therapy versus usual care alone for inflammatory bowel disease: A systematic review and meta-analysis.

Objective: Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disease that includes ulcerative colitis (UC) and Crohn's disease (CD). Hyperbaric oxygen therapy (HBOT) involves breathing pure oxygen in a pressurized environment. Existing literature suggests that HBOT may be an effective therapy for IBD, but a quantitative analysis is lacking. This study aims to estimate the adjunctive role of HBOT in treating IBD and lowering its recurrence rate. Design: Systematic review and meta-analysis. Methods: The Cochrane Library, EMBASE, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang databases were systematically searched by two reviewers independently. Meta-analyses were performed using Review Manager (RevMan, version 5.3). A random-effects model was applied due to the heterogeneity between studies. Results: Twenty-nine out of the initially identified 606 articles were covered in this review, with a total of 2151 patients (2071 for UC and 80 for CD). No randomized data of HBOT for CD were included. Among UC patients, usual care plus HBOT were more likely to achieve a clinical response than usual care alone (risk ratio [RR], 1.24; 95% confidence interval (CI), 1.17 to 1.31; P < 0.001). Subgroup analysis showed that the number of HBOT sessions had no statistically significant effect on overall efficacy (P > 0.05). The pooled data showed a lower recurrence rate in the usual care plus HBOT group (RR, 0.35; 95% CI, 0.24 to 0.53; P < 0.001). The standardized mean difference in the serum tumor necrosis factor level between HBOT and non-HBOT groups was -2.13 (95% CI, -3.09 to -1.18; P < 0.001). No severe adverse events of HBOT were observed. Conclusions: HBOT might be an effective and safe adjunctive treatment for IBD. Further studies are required to investigate the optimal protocol of HBOT in IBD treatment.

Ceratopteris chunii and Ceratopteris chingii (Pteridaceae), two new diploid species from China, based on morphological, cytological, and molecular data.

Understanding how natural hybridization and polyploidizations originate in plants requires identifying potential diploid ancestors. However, cryptic plant species are widespread, particularly in Ceratopteris (Pteridaceae). Identifying Ceratopteris cryptic species with different polyploidy levels is a challenge because Ceratopteris spp. exhibit high degrees of phenotypic plasticity. Here, two new cryptic species of Ceratopteris, Ceratopteris chunii and Ceratopteris chingii, are described and illustrated. Phylogenetic analyses reveal that each of the new species form a well-supported clade. C. chunii and C. chingii are similar to Ceratopteris gaudichaudii var. vulgaris and C. pteridoides, respectively, but distinct from their relatives in the stipe, basal pinna of the sterile leaf or subelliptic shape of the fertile leaf, as well as the spore surface. In addition, chromosome studies indicate that C. chunii and C. chingii are both diploid. These findings will help us further understand the origin of Ceratopteris polyploids in Asia.

[Clinical Characteristics and Risk Factors of Nosocomial Infection in 472 Patients with Non-Hodgkin Lymphoma].

OBJECTIVE: To investigate the clinical characteristics and risk factors of nosocomial infection in patients with non-Hodgkin lymphoma (NHL), in order to guide better clinical prevention and treatment of nosocomial infection. METHODS: The incidence of nosocomial infection, infection site, characteristics of pathogenic bacteria, drug sensitivity test results and infection risk factors of 472 non-Hodgkin lymphoma patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to September 2020 were retrospectively analyzed. RESULTS: Among the 472 patients, 97 (20.6%) had nosocomial infection, mainly in the lower respiratory tract (41.2%), followed by oral cavity, upper respiratory tract, urogenital tract, and blood. A total of 71 strains of pathogenic bacteria were isolated, including Gram-negative (G-) bacteria (52.1%), Gram-positive (G+) bacteria (28.2%), and fungi (19.7%). The detection rate of extended-spectrum ß-lactamase (ESBLs) in Klebsiella pneumoniae and Escherichia coli was 36.4% and 22.2%, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenems (imipenem) in G- bacteria was 33.3%, while the sensitivity rate of other G- bacteria was 100%. Among the 7 strains of Staphylococcus aureus, 1 strain was found to be methicillin-resistant Staphylococcus aureus (MRSA), and the sensitivity of G+ bacteria to linezolid, tigecyclinetegacycline and vancomycin was 100%. Candida albicans was the main source of fungal infection. Univariate analysis showed that nosocomial infection was associated with hospital day, bone marrow involvement, clinical stage, chemotherapy, neutrophil count in peripheral blood, and lymphoma type. Multivariable Logistic regression model showed that hospital days ≤7 was the protective factor of nosocomial infection, while clinical stage (Ⅲ, Ⅳ period), tumor involving bone marrow, and peripheral blood neutrophil count <0.5×109/L were major risk factors. CONCLUSION: NHL patients show high nosocomial infection rate and lower respiratory tract infection is common. Hospital day, clinical stage, presence of bone marrow invasion, and neutrophil count in peripheral blood are independent risk factors.

[Clinicopathological Features of Follicular Dendritic Cell Sarcoma].

Objective To explore the clinicopathological and immunohistochemical characteristics of follicular dendritic cell sarcoma(FDCS)and the expressions of IgG and IgG4. Methods We retrospectively analyzed the clinicopathological and immunohistochemical data of 9 pathologically confirmed FDCS cases in Peking Union Medical College Hospital from January 2005 to December 2018.Immunohistochemical staining of IgG and IgG4 were performed,and Epstein-Barr virus(EBV)-encoded RNA(EBER)in situ hybridization were carried out. Results Nine cases of FDCS included 4 men and 5 women aged 16-53 years [mean(38.2±9.7)years].The clinical manifestations included masses,lymph node enlargement,rash,and fever.The tumors were located in lymph node,retroperitoneal region,adrenal gland,neck,axillary region,and liver,respectively.Ultrasound showed clear boundary cystic or solid mass with maximum diameters of 1.5-15.0 cm.Microscopically,the spindle tumor cells were arranged in solid and storiform patterns with abundant and slightly stained cytoplasm,vacuolated nuclei,and small nucleoli.The mitosis was 1-3/10 high power fields,and necrosis was found in 5 cases.Immunohistochemically,the tumor cells were positive for CD21(6/9),CD35(6/9),and CD23(7/9). Conclusions FDCS is a rare malignant tumor,which is easy to be missed.The combination of CD21,CD35,and CD23 is helpful for diagnosis.Hyaline-vascular type Castleman's disease may be the precursor of FDCS,and there may be only a small number of IgG4-positive plasma cells in FDCS.Surgical resection remains the main treatment for FDCS.

Dose Volume Effect of Acute Diarrhea in Post-Operative Radiation for Gynecologic Cancer.

BACKGROUND: Diarrhea is the primary symptom of concern in acute post-operative radiation-induced enteritis in gynecologic cancer. We retrospectively studied the correlation between the volume of irradiated small bowel and the development of acute diarrhea in these patients. MATERIALS AND METHODS: A total of 100 post-operative gynecologic cancer patients were analyzed. Pelvic computed tomography was performed to calculate the volume of irradiated small bowel. A dose-volume histogram was calculated from 5 to 40 Gy at 5 Gy intervals. Patients receiving conventional whole pelvic radiation therapy (RT) were assigned to Group I, and those who received intensity-modulated RT (IMRT) were assigned to Group II. A total dose of 40-50 Gy was delivered at 1.8-2.0 Gy per fraction daily. Acute diarrhea during treatment was scored. All data were expressed as a mean ± standard deviation. Different dose-volume parameters for small bowel in Grades 0-1 and Grades 2-3 diarrhea were calculated by the independent t-test. Univariate analysis of diarrhea risk factors was performed with the independent t-test or Chi-square/Fisher exact test. RESULTS: Of the 77 patients who received conventional RT, 44 (57.14%) experienced Grades 2-3 toxicities. Of the 23 patients who received IMRT, 9 (39.13%) experienced Grades 2-3 toxicities. Concurrent chemotherapy was slightly associated with a higher damage score in both groups (p = 0.028). None of the patient factors (weight, percentage depth dosage, dose fraction, distance from skin to tumor, lymph node metastasis, chemotherapy, block, brachytherapy, hypertension, or diabetes) were correlated with diarrhea in the two groups. The volumes of irradiated small bowel in patients who experienced Grades 2-3 diarrhea were significantly larger than those in patients who experienced Grades 0-1 diarrhea at all dose levels in Group I. V20 (372.19 ± 133.26 cm3, p = 0.004) was an independent factor for developing Grades 2-3 diarrhea in Group I. V25 (290.35 ± 130.22 cm3, p = 0.001) was an independent risk factor for all patients who developed higher score diarrhea. CONCLUSIONS: The volume of irradiated small bowel was an independent risk factor for all patients who developed diarrhea, especially those undergoing conventional RT.

Novel far-visible and near-infrared pH probes based on styrylcyanine for imaging intracellular pH in live cells.

Two novel vis-NIR pH probes based on styrylcyanine with acidic pH response are easily synthesized, which display large Stokes shift and high sensitivity. The significant colocalizations of two probes with LysoTracker Green DND-26 are achieved in C6 cells, suggesting potential application for imaging acidic organelles in live cells.

Multifunctional imaging probe based on gadofulleride nanoplatform.

A FAR over-expressed tumor targeting multifunctional imaging probe has been fabricated based on gadofulleride nanoplatform. The combination of highly efficient MRI contrast enhancement and sensitive fluorescence imaging along with the preferential uptake toward FAR tumor cells suggest that the obtained multifunctional imaging probe possesses complementary capabilities for anatomical resolution and detection sensitivity.

MTDH/AEG-1-based DNA vaccine suppresses lung metastasis and enhances chemosensitivity to doxorubicin in breast cancer.

The gene MTDH/AEG-1 is overexpressed in more than 40% of breast cancer patients, and it is associated with poor clinical outcomes. Previous studies have indicated that MTDH/AEG-1 could promote metastatic lung-seeding and enhance chemoresistance. Therefore, MTDH/AEG-1 could be a candidate target against breast cancer lung metastasis. We demonstrated that MTDH/AEG-1-based DNA vaccine, delivered by attenuated Salmonella typhimurium, could evoke strong CD8(+) cytotoxic-T-cell mediated immune responses against breast cancer. This vaccine showed anti-tumor growth and metastasis efficacy in a prophylactic setting. Importantly, in a therapeutic model, MTDH/AEG-1 vaccine was proved to increase chemosensitivity to doxorubicin and inhibit breast cancer lung metastasis. This vaccine could also prolong the life span of tumor-bearing mice without significant side effects in vivo. These results suggested that this novel DNA vaccine was effective in the inhibition of breast cancer growth and metastasis, and this vaccine in combination with chemotherapies offered new strategies for the clinical therapeutics of breast cancer metastasis.

A novel water-soluble gossypol derivative increases chemotherapeutic sensitivity and promotes growth inhibition in colon cancer.

Compound 1 ((-)-gossypol) has been long known as a chemical anticancer agent. With its low water solubility and toxicity, it is not widely used as a commercial drug. To overcome these disadvantages, several novel derivatives of gossypol were designed, synthesized, and analyzed. One of the derivatives, compound 7 (6-aminopenicillanic acid sodium-gossypolone), was identified with great water solubility and anticancer property, suggested by inducing a dramatically decrease in Bcl-2 and Bcl-xL protein expression level found in vitro and growth inhibition of murine colon tumor in vivo. Furthermore, it was also recognized with less toxicity than compound 1 in vivo and significantly increased chemotherapeutic sensitivity against colon cancer in combination with traditional chemotherapeutic agent 5-fluorouracil. Therefore, it is concluded that compound 7 is superior to parent compound 1, and further preclinical studies of compound 7 is necessary for colon cancer therapy.

Rig-I-/- mice develop colitis associated with downregulation of G alpha i2.

RIG-I (retinoid acid-inducible gene-I), a putative RNA helicase with a cytoplasmic caspase-recruitment domain (CARD), was identified as a pattern-recognition receptor (PRR) that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I(-/-) mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I(-/-) mice are viable and fertile. Histological analysis shows that Rig-I(-/-) mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer's patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation of T-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein alpha i2 subunit (G alpha i2) in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated G alpha i2 expression. Moreover, G alpha i2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of G alpha i2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of G alpha i2 and disturbed T-cell homeostasis.